Alleviative Effect of Geniposide on Lipopolysaccharide-Stimulated Macrophages via Calcium Pathway.

In this study, we investigated how geniposide (a bioactive ingredient of gardenia fruit) acts on lipopolysaccharide (LPS)-stimulated macrophages. Griess reagent assay, Fluo-4 calcium assay, dihydrorhodamine 123 assay, multiplex cytokine assay, quantitative RT-PCR, and flow cytometry assay were used for this study. Data showed that geniposide at concentrations of 10, 25, and 50 µM reduced significantly the levels of nitric oxide, intracellular Ca2+, and hydrogen peroxide in LPS-activated RAW 264.7. Multiplex cytokine assay showed that geniposide at concentrations of 10, 25, and 50 µM meaningfully suppressed levels of IL-6, G-CSF, MCP-1, and MIP-1α in RAW 264.7 provoked by LPS; additionally, geniposide at concentrations of 25 and 50 µM meaningfully suppressed the levels of TNF-α, IP-10, GM-CSF, and MIP-1ß. Flow cytometry assay showed that geniposide reduces significantly the level of activated P38 MAPK in RAW 264.7 provoked by LPS. Geniposide meaningfully suppressed LPS-induced transcription of inflammatory target genes, such as Chop, Jak2, Fas, c-Jun, c-Fos, Stat3, Nos2, Ptgs2, Gadd34, Asc, Xbp1, Nlrp3, and Par-2. Taken together, geniposide exerts alleviative effects in LPS-stimulated macrophages via the calcium pathway.

Cervical enamel projections from a periodontal perspective: A scoping review.

Cervical enamel projections (CEPs) represent a unique developmental and anatomical anomaly wherein the enamel structure extends apically beyond the cemento-enamel junction of the tooth. In this scoping review, the existing literature on CEPs was evaluated to delineate their characteristics, prevalence, predilection for specific teeth and surfaces, clinical significance, and management approaches. Searches were conducted on MEDLINE (PubMed), Cochrane Library, and Embase databases using the keywords "enamel projection(s)" or "ectopic enamel." In total, 24 studies meeting inclusion criteria were included in the review. The prevalence of CEPs varied widely (8.3%-85.1%), predominantly manifesting as grade I or grade III. Mandibular first and second molars exhibited a higher incidence of CEPs, with a notable predilection for buccal surfaces. The consensus in most studies was that CEPs are associated with localized periodontal diseases. Recommendations inclined toward the removal of ectopic enamel during periodontal surgery to enhance periodontal attachment formation. However, decision-making should involve careful consideration of the benefits and drawbacks based on individual circumstances.

Choosing the right adjuvant therapy for stage III-IVA endometrial cancer: A comparative analysis of chemoradiotherapy and chemotherapy.

OBJECTIVE: The optimal adjuvant treatment for patients with locally advanced endometrial cancer (EC) remains debatable. We comparatively analyzed recurrence patterns and survival outcomes in patients with stage III-IVA EC treated with adjuvant chemotherapy (CT) exclusively or combined with radiotherapy (CRT). METHODS: We retrospectively analyzed 184 patients treated for stage III-IVA EC at 2 tertiary institutions between 2010 and 2021. All patients underwent standard primary surgery and received either CT alone (n = 89) or CRT (n = 95) as an adjuvant treatment. We compared the failure patterns, recurrence-free survival (RFS), and overall survival (OS) between the CT and CRT groups. RESULTS: The median follow-up period was 54.8 months. Most patients underwent pelvic (94.6%) or para-aortic (75.5%) lymphadenectomies. The 5-year RFS was 69.2% with CRT versus 56.3% with CT (P = 0.038), and 5-year OS was 86.1% versus 78.9% (P = 0.357). Pelvic and para-aortic recurrence rates were significantly higher in the CT group (pelvic: 29.2%; para-aortic: 20.2%) than in the CRT group (pelvic: 10.5%; para-aortic: 6.3%). The CRT group showed a higher rate of distant recurrence (CRT, 23.2% vs. CT, 14.6%) however, the 5-year cumulative incidence of distant recurrence was not significantly different between the two groups (CRT, 28% vs. CT, 35%). CONCLUSIONS: This study highlights the potential benefits of adjuvant CRT in patients with stage III-IVA EC. The incorporation of molecular classification is necessary to derive optimal personalized adjuvant treatment strategies for this patient population.

Assessment of Bone Marrow Involvement in Extranodal NK/T-Cell Lymphoma: Positron Emission Tomography versus Bone Marrow Biopsy, and the Significance of Minimal Involvement by EBV+ Cells (KROG 18-09).

PURPOSE: This study aims to investigate the diagnostic significance of positron emission tomography/computed tomography (PET/CT) in assessing bone marrow (BM) involvement through a comparison of PET/CT findings with BM biopsy in extranodal natural killer/T-cell lymphoma. MATERIALS AND METHODS: The medical records of 193 patients were retrospectively reviewed. Patients were categorized as having early-stage (PET-ES) or advanced-stage (PET-AS) disease based on PET/CT results. The BM involvement was classified into three groups according to BM biopsy: gross BM involvement, minimal BM involvement (defined as the presence of a limited number of Epstein-Barr virus-positive cells in BM), and no involvement. Calculations of the accuracy of PET/CT in detecting BM involvement and analysis of the clinical outcomes (progression-free survival [PFS] and overall survival [OS]) according to the BM biopsy status were performed. RESULTS: PET/CT exhibited a sensitivity of 64.7% and a specificity of 96.0% in detecting gross BM involvement. For detecting any (both gross and minimal) BM involvement, the sensitivity was 30.4%, while the specificity was 99.0%. Only one patient (0.7%) demonstrated gross BM involvement among the PET-ES group. Survival outcomes of the PET-ES group with minimal BM involvement (3-year PFS, 55.6%; OS, 77.0%) were closer to those of the PET-ES group with no BM involvement (3-year PFS, 62.2%; OS, 80.6%) than to those of the PET-AS group (3-year PFS, 20.1%; OS, 29.9%). CONCLUSION: PET/CT exhibits high specificity, but moderate and low sensitivity in detecting gross and minimal BM involvement, respectively. The clinical significance of minimal BM involvement for patients in the PET-ES group may be limited.

Altered cortical thickness of the superior frontal gyrus and fusiform gyrus in individuals with subthreshold social anxiety.

Subthreshold social anxiety (SSA) is a condition in which individuals experience social anxiety that does not reach the threshold required for a clinical diagnosis of a social anxiety disorder (SAD). Although SSA may not impair lives as severely as SAD, it can affect social functioning. However, only a few studies focused on structural neural correlates of SSA. We recruited 65 individuals with SSA and used the Leibowitz Social Anxiety Scale to assess their social and performance anxiety levels and other relevant measures of social anxiety. Voxel-wise whole-brain correlational analyses showed a positive association between the cortical thickness (CT) of the superior frontal gyrus (SFG) and social anxiety levels and a negative correlation between the CT of the fusiform gyrus (FG) and performance anxiety levels in individuals with SSA. Exploratory Pearson's correlation analyses showed significant positive correlations between the CT of the SFG and Generalized Anxiety Disorder-7 total scores and negative associations between the CT of the FG and Beck Anxiety Inventory total scores. Our study provides insight into the neural basis of SSA, particularly performance anxiety, by highlighting the association between CT in specific brain regions and SSA characteristics.

Capsaicin supplementation prevents western diet-induced hyperleptinemia by reducing endoplasmic reticulum stress in apolipoprotein E-deficient mice.

Background: Endoplasmic reticulum (ER) stress implicated in leptin resistance in the diet-induced obesity, which can accelerate the development of atherosclerosis forms the background of this study. Objective: This study aimed to investigate the effect of capsaicin on hyperleptinema by inhibiting ER stress in apolipoprotein E-deficient (ApoE-/-) mice fed a western diet (WD). Design: ApoE -/- mice were assigned one of three experimental diets: WD (60% kcal from fat, n = 10), WD + 0.015% capsaicin (n = 10, w/w), and WD + 1% PBA (n = 10, w/w) for 12 weeks. Results: In metabolic parameters, supplementation of dietary capsaicin displayed marked reduction of body weight gain and adipose tissue weight, plasma leptin, total cholesterol, and hepatic triglyceride levels without change in the plasma insulin level compared with WD fed ApoE-/- mice after 12 weeks. Capsaicin supplementation also attenuated the protein expression of ER stress markers such as eukaryotic translational initiation factor 2α and C/EBP homology protein in the liver, as well as glucose-related protein 78 localization in the aorta, indicating that capsaicin inhibits diet-induced hyperleptinemia in part by regulating the protein expression involved in ER stress. Conclusion: Capsaicin, therefore, may have potential as a therapeutic agent for individuals with diet-induced hyperleptinemia.

Differential impacts of reduced worktime on work-life balance in Korea.

This study analyzes the heterogenous effects of reducing weekly work hour on workers' quality of life in Korea. Using longitudinal household data from the Korean Labor and Income Panel Study (KLIPS) from 2001 to 2017, this study aims to shed light on how the work hour reduction policy may differently affect workers with different levels of resources and support by demographic and socioeconomic status. Our estimates from the difference-in-differences approach exploiting the staggered implementation of the work hour reduction policy indicate that the policy increased leisure satisfaction of female workers with low educational level and female workers in regular or inflexible work setting. Given Korea's exceedingly long working hours and inequities in the labor market, a better understanding of the complex factors that affect work-life balance can be helpful in developing policies supportive of healthy work-life balance for workers. This study, to our knowledge, is the first to investigate the composition of workers in the Korean labor market and examine differential impacts of the workhour reduction policy by demographic and socioeconomic status.

Supplementary Effects of Allium hookeri Extract on Glucose Tolerance in Prediabetic Subjects and C57BL/KsJ-db/db Mice.

Allium hookeri (AH) has been used as a nutritional and medicinal food in Asia for many years. Our previous studies have described its anti-diabetic, anti-obesity, and anti-inflammatory activities in animal models and prediabetes. This study investigated whether AH could improve glycemia by modulating insulin secretion in prediabetic subjects through an in-depth study. Eighty prediabetic subjects (100 ≤ fasting plasma glucose < 140 mg/dL) were randomly assigned to a placebo (n = 40) group or an ethanol AH extract (500 mg/day, n = 40) group for 12 weeks. Dietary intake and physical activity, blood glucose (an oral glucose tolerance test for 120 min), insulin (insulin response to oral glucose for 120 min), area under the curve (AUC) of glucose or insulin after oral glucose intake, insulin sensitivity markers, C-peptide, adiponectin, glycated hemoglobin A1c (HbA1c) levels, hematological tests (WBC, RBC, hemoglobin, hematocrit, and platelet count), blood biochemical parameters (ALP, AST, total bilirubin, total protein, albumin, gamma-GT, BUN, creatinine, LD, CK, and hs-CRP), and urine parameters (specific gravity and pH) were examined at both baseline and 12 weeks after supplementation with placebo or AH capsules. Fifty-eight participants (placebo group: 20 men and 10 women; AH group: 13 men and 15 women) completed the study. AH supplementation moderately reduced postprandial blood glucose at 60 min (-6.14 mg/dL, p = 0.061), postprandial insulin levels at 90 min (-16.69 µU/mL, p = 0.017), the glucose AUC at 90 min (-412.52 mg*min/dL, p = 0.021), as well as the insulin AUC at 90 min (-978.77 µU*min/mL, p = 0.021) and 120 min (-1426.41 µU*min/mL, p = 0.015) when compared with the placebo group. However, there were no effects of AH on dietary intake and physical activity; HOMA index; HbAlc; C-peptide; or adiponectin, hematological-, blood biochemical-, and urinary markers. To confirm the effects of AH extract on blood glucose insulin sensitivity, C57BL/6J or C57BL/KsJ-db/db mice were used (n = 8/group). Body weight, fasting plasma glucose level, lipid profiles, liver and renal function, pancreatic histology, and insulin immunoreactivity were assessed. In the diabetic db/db mice, hyperglycemia, which was accompanied by an increase in insulin secretion in diabetic mice, was significantly reduced by AH treatment, resulting in the alleviation of ß-cell overcompensation and insulin resistance. We confirmed that AH supplementation can effectively control blood glucose and insulin levels by improving insulin sensitivity and may be a potential agent for glycemic control in subjects with prediabetes and type 2 diabetes mellitus.

Experiences Pertaining to Successful Aging in Middle-Aged Women in South Korea.

This study aimed to analyze and gain an in-depth understanding of the experiences pertaining to successful aging in middle-aged women in South Korea. A sample of 12 middle-aged women, capable of sharing their lived experiences, was divided into three age-based groups: those in their 40s, those in their 50s, and those aged 60-65 years. The collected data were analyzed using Colaizzi's phenomenological method. Five theme clusters and ten themes emerged. The experiences of successful aging among middle-aged women were categorized as: "Coping with changes in the mind and body", "Financially stable life", "Undergoing the aging process with a healthy family", "Preparations for dying well", and "Pursuing a meaningful, harmonious life". These findings highlight the need for programs that prepare middle-aged women to positively accept and enjoy older adulthood by identifying and addressing the factors essential for successful aging and reducing any negative emotions attached to aging and older adulthood.

Transcriptomic analysis of the antimicrobial activity of prodigiosin against Cutibacterium acnes.

Prodigiosin, a red pigment produced by Hahella chejuensis, a marine-derived microorganism, has several biological functions, including antimicrobial activity and inflammatory relief. In this study, the antibacterial activity of prodigiosin against skin microorganisms was explored. Paper disc assay on skin bacterial cells revealed that Cutibacterium acnes related to acne vulgaris highly susceptible to prodigiosin. MIC (Minimal Inhibitory Concentration) and MBC (Minimal Bactericidal Concentration) were determined on Cutibacterium species. The RNA-seq analysis of prodigiosin-treated C. acnes cells was performed to understand the antibacterial mechanism of prodigiosin. Among changes in the expression of hundreds of genes, the expression of a stress-responsive sigma factor encoded by sigB increased. Conversely, the gene expression of cell wall biosynthesis and energy metabolism was inhibited by prodigiosin. Specifically, the expression of genes related to the metabolism of porphyrin, a pro-inflammatory metabolite, was significantly reduced. Therefore, prodigiosin could be used to control C. acnes. Our study provided new insights into the antimicrobial mechanism of prodigiosin against C. acnes strains.

The Effect of Respiratory Motion in Breast Intensity-modulated Radiation Therapy: 3D-Printed Dynamic Phantom Study.

BACKGROUND/AIM: This study evaluated the dosimetric effect of respiratory motion in intensity-modulated radiation therapy (IMRT) for breast cancer using a three-dimensional (3D)-printed dynamic phantom. MATERIALS AND METHODS: Computed tomography (CT) data from breast cancer patients were used to create a 3D-printed breast phantom. Various types of treatment plans were generated using CT images acquired at the exhalation phase. Different infill densities in the 3D-printed phantom were tested to validate their effect on simulating the average human breast tissue density. Plans were delivered to the 3D-printed dynamic phantom in the exhalation position and free-breathing motion. Dosimetric verification was performed using Gafchromic EBT3 films. RESULTS: After changing the infill density to obtain Hounsfield Unit values similar to those of human breast tissue, a realistic patient-specific breast phantom was fabricated using a 3D printer at 80% infill density. The gamma passing rates of the dose distribution delivered in the exhalation phase and free-breathing motion were 92% or more. In addition, the dynamic phantom doses with free-breathing motion were directly compared with the static phantom dose in terms of sagittal dose profiles. Gamma passing rates of >93% and 90% were achieved at 3%/3 mm and 3%/2 mm, respectively. CONCLUSION: Despite a blurred dose distribution, the dose map of the film measurement with respiratory motion could be delivered without significantly increasing the dose heterogeneity of the tumor bed or loss of target coverage. Our findings demonstrate that the impact of respiration on breast IMRT for whole-breast irradiation was not significant, even in the tumor bed.

Mesencephalic astrocyte-derived neurotrophic factor promotes axonal regeneration and the motor function recovery after sciatic nerve injury.

Peripheral nerve injuries have common clinical problems that are often accompanied by sensory and motor dysfunction and failure of axonal regeneration. Although various therapeutic approaches have been attempted, full functional recovery and axonal regeneration are rarely achieved in patients. In this study, we investigated the effects of recombinant adeno-associated virus (AAV) of mesencephalic astrocyte-derived neurotrophic factor (AAV-MANF) or placental growth factor (AAV-PlGF) transduced into mesenchymal stem cells (hMSC-MANF and hMSC-PlGF), which were then transplanted using human decellularized nerves (HDN) into sciatic nerve injury model. Our results showed that both AAV-MANF and AAV-PlGF were expressed in MSCs transplanted into the injury site. Behavioral measurements performed 2, 4, 6, 8, and 12 weeks after injury indicated that MANF facilitated the rapid and improved recovery of sensory and motor functions than PlGF. In addition, immunohistochemical analysis was used to quantitatively analyze the myelination of neurofilaments, Schwann cells, and regrowth axons. Both hMSC-MANF and hMSC-PlGF increased axon numbers and immunoreactive areas of axons and Schwann cells compared with the hMSC-GFP group. However, hMSC-MANF significantly improved the thickness of axons and Schwann cells compared with hMSC-PlGF. G-ratio analysis also showed a marked increase in axon myelination in axons thicker than 2.0 µm treated with MANF than that treated with PlGF. Our study suggests that transplantation of hMSC transduced with AAV-MANF has a potential to provide a novel and efficient strategy for promoting functional recovery and axonal regeneration in peripheral nerve injury.

Functional Role of Phospholipase D in Bone Metabolism.

Phospholipase D (PLD) proteins are major enzymes that regulate various cellular functions, such as cell growth, cell migration, membrane trafficking, and cytoskeletal dynamics. As they are responsible for such important biological functions, PLD proteins have been considered promising therapeutic targets for various diseases, including cancer and vascular and neurological diseases. Intriguingly, emerging evidence indicates that PLD1 and PLD2, 2 major mammalian PLD isoenzymes, are the key regulators of bone remodeling; this suggests that these isozymes could be used as potential therapeutic targets for bone diseases, such as osteoporosis and rheumatoid arthritis. PLD1 or PLD2 deficiency in mice can lead to decreased bone mass and dysregulated bone homeostasis. Although both mutant mice exhibit similar skeletal phenotypes, PLD1 and PLD2 play distinct and nonredundant roles in bone cell function. This review summarizes the physiological roles of PLD1 and PLD2 in bone metabolism, focusing on recent findings of the biological functions and action mechanisms of PLD1 and PLD2 in bone cells.

Self-compassion is associated with the superior longitudinal fasciculus in the mirroring network in healthy individuals.

Self-compassion (SC) involves taking an emotionally positive attitude towards oneself when suffering. Although SC has positive effects on mental well-being as well as a protective role in preventing symptoms in healthy individuals, few studies on white matter (WM) microstructures in neuroimaging studies of SC has been studied. Brain imaging data were acquired from 71 healthy participants. WM regions of mirroring network were analyzed using tract-based spatial statistics. After the WM regions associated with SC were extracted, exploratory correlation analysis with the self-forgiveness scale, the coping scale, and the world health organization quality of life scale abbreviated version was performed. We found that self-compassion scale total scores were negatively correlated with the fractional anisotropy (FA) values of the superior longitudinal fasciculus (SLF) in healthy individuals. The self-kindness and mindfulness subscale scores were also negatively correlated with FA values of the same regions. These FA values were negatively correlated with the total scores of self-forgiveness scale, and self-control coping strategy and confrontation coping strategy. Our findings suggest levels of SC may be associated with WM microstructural changes of SLF in healthy individuals. These lower WM microstructures may be associated with positive personal attitudes, such as self-forgiveness, self-control and active confrontational strategies.

Multiplex Single-Nucleotide Microbial Genome Editing Achieved by CRISPR-Cas9 Using 5'-End-Truncated sgRNAs.

Multiplex genome editing with CRISPR-Cas9 offers a cost-effective solution for time and labor savings. However, achieving high accuracy remains a challenge. In an Escherichia coli model system, we achieved highly efficient single-nucleotide level simultaneous editing of the galK and xylB genes using the 5'-end-truncated single-molecular guide RNA (sgRNA) method. Furthermore, we successfully demonstrated the simultaneous editing of three genes (galK, xylB, and srlD) at single-nucleotide resolution. To showcase practical application, we targeted the cI857 and ilvG genes in the genome of E. coli. While untruncated sgRNAs failed to produce any edited cells, the use of truncated sgRNAs allowed us to achieve simultaneous and accurate editing of these two genes with an efficiency of 30%. This enabled the edited cells to retain their lysogenic state at 42 °C and effectively alleviated l-valine toxicity. These results suggest that our truncated sgRNA method holds significant potential for widespread and practical use in synthetic biology.

Diallyl disulfide alleviates hypercholesterolemia induced by a western diet by suppressing endoplasmic reticulum stress in apolipoprotein E-deficient mice.

BACKGROUND: The endoplasmic reticulum (ER) plays a pivotal role in maintaining cellular metabolic homeostasis. ER stress refers to the accumulation of misfolded proteins, which can trigger an unfolded protein response for survival or death in the cells. Diallyl disulfide (DADS), a major active compound in garlic, has many health benefits for patients with metabolic diseases, especially cardiovascular or fatty liver diseases. However, its role in attenuating hypercholesterolemia by suppressing ER stress remains unknown. Therefore, in this study, we determined whether DADS supplementation could reduce ER stress in apolipoprotein E-deficient (ApoE-/-) mice fed a Western-type diet (WD). METHODS: ApoE-/- mice were fed either a WD alone or a WD supplemented with 0.1% DADS for 12 weeks (n = 10). Levels of plasma total cholesterol, triglyceride, leptin, and insulin were determined. Western blotting was performed to measure protein levels involved in ER stress markers. Histology and Immunostaining were performed on aortic root sections to confirm the effect of DADS on histology and expression of ER chaperone protein GRP78. RESULTS: The metabolic parameters showed that increases in fat weight, leptin resistance, and hypercholesterolemia were reversed in DADS-supplemented mice (p < 0.05). In addition, DADS ameliorated not only the protein of ER stress markers, phospho-eukaryotic initiation factor 2 subunit alpha and C/EBP homologous protein in the liver (p < 0.05) but also glucose-related protein 78 localization in the aorta. CONCLUSIONS: This indicates that DADS inhibits diet-induced hypercholesterolemia, at least in parts by regulating ER stress markers. DADS may be a good candidate for treating individuals with diet-induced hypercholesterolemia.

Radiotherapy for Diffuse Intrinsic Pontine Glioma: Insufficient but Indispensable.

Diffuse intrinsic pontine gliomas (DIPGs) account for 10%-20% of all central nervous system tumors in children and are the leading cause of death in children with brain tumors. Although many clinical trials have been conducted over the past decades, the survival outcome has remained unchanged. Over 90% of children die within 2 years of the diagnosis, and radiotherapy remains the standard treatment to date. To improve the prognosis, hyperfractionated and hypofractionated radiotherapy and/or addition of radiosensitizers have been investigated. However, none of the radiotherapy approaches have shown a survival benefit, and the overall survival of patients with DIPG is approximately 11 months. Here, we comprehensively review the management of DIPG with focus on radiotherapy.

Metformin acts as a dual glucose regulator in mouse brain.

Aims: Metformin improves glucose regulation through various mechanisms in the periphery. Our previous study revealed that oral intake of metformin activates several brain regions, including the hypothalamus, and directly activates hypothalamic S6 kinase in mice. In this study, we aimed to identify the direct effects of metformin on glucose regulation in the brain. Materials and methods: We investigated the role of metformin in peripheral glucose regulation by directly administering metformin intracerebroventricularly in mice. The effect of centrally administered metformin (central metformin) on peripheral glucose regulation was evaluated by oral or intraperitoneal glucose, insulin, and pyruvate tolerance tests. Hepatic gluconeogenesis and gastric emptying were assessed to elucidate the underlying mechanisms. Liver-specific and systemic sympathetic denervation were performed. Results: Central metformin improved the glycemic response to oral glucose load in mice compared to that in the control group, and worsened the response to intraperitoneal glucose load, indicating its dual role in peripheral glucose regulation. It lowered the ability of insulin to decrease serum glucose levels and worsened the glycemic response to pyruvate load relative to the control group. Furthermore, it increased the expression of hepatic G6pc and decreased the phosphorylation of STAT3, suggesting that central metformin increased hepatic glucose production. The effect was mediated by sympathetic nervous system activation. In contrast, it induced a significant delay in gastric emptying in mice, suggesting its potent role in suppressing intestinal glucose absorption. Conclusion: Central metformin improves glucose tolerance by delaying gastric emptying through the brain-gut axis, but at the same time worsens it by increasing hepatic glucose production via the brain-liver axis. However, with its ordinary intake, central metformin may effectively enhance its glucose-lowering effect through the brain-gut axis, which could surpass its effect on glucose regulation via the brain-liver axis.

Gender differences in anxiety and depressive symptomatology determined by network analysis in panic disorder.

BACKGROUND: It has been suggested that gender differences in anxiety and depressive symptoms characterize panic disorder (PD) in terms of vulnerability to stressful life events, anxiety, depressive symptom patterns, and brain structure. However, few studies have investigated the gender differences in PD using a network approach. METHODS: This study included 619 participants with PD (313 men). The Panic Disorder Severity Scale, Albany Panic and Phobia Questionnaire, and Beck Depression Inventory-II were used to evaluate symptomatology. To investigate the PD-related white matter (WM) neural correlates, tract-based spatial statistics were used. The PD-related clinical scales and WM neural correlates were included in the network analysis to identify associations between variables. To evaluate network differences between genders, network comparison tests were conducted. RESULTS: Our findings revealed that agoraphobia in men was the strongest central symptom. In addition, loss of pleasure, and not anxiety or panic symptoms, was the strongest central symptom in women with PD. The network comparison test revealed that the bridge strength score was higher in agoraphobia and tiredness in men and in self-criticalness in women. Furthermore, in the network that includes neural correlates of WM, the bridge strength score was higher in the cingulate gyrus WM in men and the cingulum hippocampus in women. LIMITATIONS: Since this is a cross-sectional network study of PD patients, the causal relationship between interactions in this network analysis for both genders may not be accurately determined. CONCLUSION: Network structures of anxiety and depressive symptomatology and related WM neural correlates can differ according to gender in PD patients.